Between June 1999 and September 2002, 45 patients (age, 34 +/- 13 years; mean shunt ratio, 2.6 +/- 0.6) underwent transcatheter atrial septal defect (ASD) closure at our institution with the Amplatzer septal occluder (mean device size, 31.4 +/- 3 mm). Patients were selected by transesophageal echocardiography. The mean ASD dimension was 25.3 +/- 3.7 mm and 33 (73%) patients had deficient anterior rim. Specific procedural details included the use of 13 or 14 Fr introducer sheaths and the right upper pulmonary vein approach if the conventional approach failed. There were two procedural failures, with device embolization in both (surgical retrieval in one, catheter retrieval in one). During follow-up (3-30 months; median, 16 months), one patient (59 years) with previous atrial flutter had pulmonary embolism and was managed with anticoagulation. Two patients developed symptomatic atrial flutter. Fluoroscopy time was 31.6 +/- 19.5 min for the first 22 cases and 19.6 +/- 11.4 min for the rest (P = 0.04). Transcatheter closure of large ASDs is technically feasible but careful long-term follow-up is needed to document its safety.